The Effects of PMM2-CDG-Causing Mutations on the Folding, Activity, and Stability of the PMM2 Protein

Human Mutation

Volumn 36, Issue 9, 2015, Pages 851-860

  Yuste Checa, Patricia ^a,b   Gámez, Alejandra ^a,b   Brasil, Sandra ^a,b   Desviat, Lourdes R ^a,b   Ugarte, Magdalena ^a,b   Pérez Cerdá, Celia ^a,b   Pérez, Belén ^a,b  

^a CSIC   (Spain)

^b HOSPITAL UNIVERSITARIO LA PAZ IDIPAZ   (Spain)

Author keywords

Congenital disorders of glycosylation; Phosphomannomutase 2; PMM2; PMM2 CDG; Protein stability

Indexed keywords

PHOSPHOMANNOMUTASE; PHOSPHOMANNOMUTASE 2; UNCLASSIFIED DRUG; HYBRID PROTEIN; MUTASE; PHOSPHOMANNOMUTASE 2, HUMAN;

ARTICLE; CONTROLLED STUDY; DIMERIZATION; ENZYME ACTIVITY; ENZYME STABILITY; FLUOROMETRY; GENE EXPRESSION; GENE EXPRESSION SYSTEM; HALF LIFE TIME; INCUBATION TIME; LOSS OF FUNCTION MUTATION; MOLECULAR WEIGHT; MUTATION; OLIGOMERIZATION; PRIORITY JOURNAL; PROTEIN FOLDING; PROTEIN HOMEOSTASIS; PROTEIN PURIFICATION; PROTEIN STABILITY; PROTEIN UNFOLDING; STEADY STATE; THERMOSTABILITY; ANIMAL; CHEMISTRY; CONGENITAL DISORDER OF GLYCOSYLATION; ENZYME ACTIVATION; FIBROBLAST; GENETICS; HUMAN; METABOLISM; MOUSE; PROTEIN DEGRADATION; PROTEIN MULTIMERIZATION;

BACTERIA (MICROORGANISMS); EUKARYOTA; MURINAE;

ANIMALS; CONGENITAL DISORDERS OF GLYCOSYLATION; ENZYME ACTIVATION; ENZYME STABILITY; FIBROBLASTS; GENE EXPRESSION; HUMANS; MICE; MUTATION; PHOSPHOTRANSFERASES (PHOSPHOMUTASES); PROTEIN FOLDING; PROTEIN MULTIMERIZATION; PROTEOLYSIS; RECOMBINANT FUSION PROTEINS;

EID: 84938973394     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.22817     Document Type: Article

References (42)

1. Bradford MM. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248-254.
2. Briones P, Vilaseca MA, Schollen E, Ferrer I, Maties M, Busquets C, Artuch R, Gort L, Marco M, van Schaftingen E, Matthijs G, Jaeken J, Chabas A. 2002. Biochemical and molecular studies in 26 Spanish patients with congenital disorder of glycosylation type Ia. J Inherit Metab Dis 25:635-646.
3. Casado M, O'Callaghan MM, Montero R, Perez-Cerda C, Perez B, Briones P, Quintana E, Muchart J, Aracil A, Pineda M, Artuch R. 2012. Mild clinical and biochemical phenotype in two patients with PMM2-CDG (congenital disorder of glycosylation Ia). Cerebellum 11:557-563.
4. Cline A, Gao N, Flanagan-Steet H, Sharma V, Rosa S, Sonon R, Azadi P, Sadler KC, Freeze HH, Lehrman MA, Steet R. 2012. A zebrafish model of PMM2-CDG reveals altered neurogenesis and a substrate-accumulation mechanism for N-linked glycosylation deficiency. Mol Biol Cell 23:4175-4187.
5. Cylwik B, Naklicki M, Chrostek L, Gruszewska E. 2013. Congenital disorders of glycosylation. Part I. Defects of protein N-glycosylation. Acta Biochim Polym 60:151-161.
6. de Koning TJ, Dorland L, van Diggelen OP, Boonman AM, de Jong GJ, van Noort WL, De Schryver J, Duran M, van den Berg IE, Gerwig GJ, Berger R, Poll-The Bt. 1998. A novel disorder of N-glycosylation due to phosphomannose isomerase deficiency. Biochem Biophys Res Commun 245:38-42.
7. Eklund EA, Merbouh N, Ichikawa M, Nishikawa A, Clima JM, Dorman JA, Norberg T, Freeze HH. 2005. Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts. Glycobiology 15:1084-1093.
8. Foulquier F, Amyere M, Jaeken J, Zeevaert R, Schollen E, Race V, Bammens R, Morelle W, Rosnoblet C, Legrand D, Demaegd D, Buist N, et al. 2012. TMEM165 deficiency causes a congenital disorder of glycosylation. Am J Hum Genet 91:15-26.
9. Freeze HH. 2006. Genetic defects in the human glycome. Nat Rev Genet 7:537-551.
10. Freeze HH. 2009. Towards a therapy for phosphomannomutase 2 deficiency, the defect in CDG-Ia patients. Biochim Biophys Acta 1792:835-840.
11. Freeze HH, Chong JX, Bamshad MJ, Ng BG. 2014. Solving glycosylation disorders: fundamental approaches reveal complicated pathways. Am J Hum Genet 94:161-175.
12. Giurgea I, Michel A, LeMerrer M, Seta N, de Lonlay P. 2005. Underdiagnosis of mild congenital disorders of glycosylation type Ia. Pediatr Neurol 32:121-123.
13. Gregersen N, Bross P, Vang S, Christensen JH. 2006. Protein misfolding and human disease. Annu Rev Genomics Hum Genet 7:103-124.
14. Grunewald S, Schollen E, Van Schaftingen E, Jaeken J, Matthijs G. 2001. High residual activity of PMM2 in patients' fibroblasts: possible pitfall in the diagnosis of CDG-Ia (phosphomannomutase deficiency). Am J Hum Genet 68:347-354.
15. Hardre R, Khaled A, Willemetz A, Dupre T, Moore S, Gravier-Pelletier C, Le Merrer Y. 2007. Mono, di and tri-mannopyranosyl phosphates as mannose-1-phosphate prodrugs for potential CDG-Ia therapy. Bioorg Med Chem Lett 17:152-155.
16. Hennet T. 2012. Diseases of glycosylation beyond classical congenital disorders of glycosylation. Biochim Biophys Acta 1820:1306-1317.
17. Jaeken J, Matthijs G. 2007. Congenital disorders of glycosylation: a rapidly expanding disease family. Annu Rev Genomics Hum Genet 8:261-278.
18. Kjaergaard S, Skovby F, Schwartz M. 1998. Absence of homozygosity for predominant mutations in PMM2 in Danish patients with carbohydrate-deficient glycoprotein syndrome type 1. Eur J Hum Genet 6:331-336.
19. Le Bizec C, Vuillaumier-Barrot S, Barnier A, Dupre T, Durand G, Seta N. 2005. A new insight into PMM2 mutations in the French population. Hum Mutat 25:504-505.
20. Martinez A, Calvo AC, Teigen K, Pey AL. 2008. Rescuing proteins of low kinetic stability by chaperones and natural ligands phenylketonuria, a case study. Prog Mol Biol Transl Sci 83:89-134.
21. Matthijs G, Schollen E, Pardon E, Veiga-Da-Cunha M, Jaeken J, Cassiman JJ, Van Schaftingen E. 1997. Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome). Nat Genet 16:88-92.
22. Matthijs G, Schollen E, Van Schaftingen E, Cassiman JJ, Jaeken J. 1998. Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A. Am J Hum Genet 62:542-550.
23. Muntau AC, Leandro J, Staudigl M, Mayer F, Gersting SW. 2014. Innovative strategies to treat protein misfolding in inborn errors of metabolism: pharmacological chaperones and proteostasis regulators. J Inherit Metab Dis 37:505-523.
24. Niesen FH, Berglund H, Vedadi M. 2007. The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat Protoc 2:2212-2221.
25. Perez B, Briones P, Quelhas D, Artuch R, Vega AI, Quintana E, Gort L, Ecay MJ, Matthijs G, Ugarte M, Perez-Cerda C. 2011. The molecular landscape of phosphomannose mutase deficiency in iberian peninsula: identification of 15 population-specific mutations. JIMD Rep 1:117-123.
26. Pey AL, Ying M, Cremades N, Velazquez-Campoy A, Scherer T, Thony B, Sancho J, Martinez A. 2008. Identification of pharmacological chaperones as potential therapeutic agents to treat phenylketonuria. J Clin Invest 118:2858-2867.
27. Quelhas D, Quental R, Vilarinho L, Amorim A, Azevedo L. 2007. Congenital disorder of glycosylation type Ia: searching for the origin of common mutations in PMM2. Ann Hum Genet 71(Pt 3):348-353.
28. Richard E, Desviat LR, Ugarte M, Perez B. 2013. Oxidative stress and apoptosis in homocystinuria patients with genetic remethylation defects. J Cell Biochem 114:183-191.
29. Schneider A, Thiel C, Rindermann J, DeRossi C, Popovici D, Hoffmann GF, Grone HJ, Korner C. 2012. Successful prenatal mannose treatment for congenital disorder of glycosylation-Ia in mice. Nat Med 18:71-73.
30. Schollen E, Keldermans L, Foulquier F, Briones P, Chabas A, Sanchez-Valverde F, Adamowicz M, Pronicka E, Wevers R, Matthijs G. 2007. Characterization of two unusual truncating PMM2 mutations in two CDG-Ia patients. Mol Genet Metab 90:408-413.
31. Schymkowitz J, Borg J, Stricher F, Nys R, Rousseau F, Serrano L. 2005a. The FoldX web server: an online force field. Nucleic Acids Res 33(Web Server issue):W382-W388.
32. Schymkowitz JW, Rousseau F, Martins IC, Ferkinghoff-Borg J, Stricher F, Serrano L. 2005b. Prediction of water and metal binding sites and their affinities by using the Fold-X force field. Proc Natl Acad Sci USA 102:10147-10152.
33. Sharma V, Ichikawa M, Freeze HH. 2014a. Mannose metabolism: more than meets the eye. Biochem Biophys Res Commun 453:220-228.
34. Sharma V, Nayak J, DeRossi C, Charbono A, Ichikawa M, Ng BG, Grajales-Esquivel E, Srivastava A, Wang L, He P, Scott DA, Russel J et al. 2014b. Mannose supplements induce embryonic lethality and blindness in phosphomannose isomerase hypomorphic mice. FASEB J 28:1854-1869.
35. Silvaggi NR, Zhang C, Lu Z, Dai J, Dunaway-Mariano D, Allen KN. 2006. The X-ray crystal structures of human alpha-phosphomannomutase 1 reveal the structural basis of congenital disorder of glycosylation type 1a. J Biol Chem 281:14918-14926.
36. Stenson PD, Mort M, Ball EV, Shaw K, Phillips A, Cooper DN. 2014. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum Genet 133:1-9.
37. Studier FW. 2005. Protein production by auto-induction in high density shaking cultures. Protein Expr Purif 41:207-234.
38. Thiel C, Lubke T, Matthijs G, vonFigura K, Korner C. 2006. Targeted disruption of the mouse phosphomannomutase 2 gene causes early embryonic lethality. Mol Cell Biol 26:5615-5620.
39. Underhaug J, Aubi O, Martinez A. 2012. Phenylalanine hydroxylase misfolding and pharmacological chaperones. Curr Top Med Chem 12:2534-2545.
40. Van Schaftingen E, Jaeken J. 1995. Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein syndrome type I. FEBS Lett 377:318-320.
41. Vega AI, Perez-Cerda C, Abia D, Gamez A, Briones P, Artuch R, Desviat LR, Ugarte M, Perez B. 2011. Expression analysis revealing destabilizing mutations in phosphomannomutase 2 deficiency (PMM2-CDG): expression analysis of PMM2-CDG mutations. J Inherit Metab Dis 34:929-939.
42. Westphal V, Kjaergaard S, Schollen E, Martens K, Grunewald S, Schwartz M, Matthijs G, Freeze HH. 2002. A frequent mild mutation in ALG6 may exacerbate the clinical severity of patients with congenital disorder of glycosylation Ia (CDG-Ia) caused by phosphomannomutase deficiency. Hum Mol Genet 11:599-604.